Outcomes and Safety of PD-1 Blockades Plus Anlotinib Regimen in Previously-Treated Metastatic Esophageal Squamous Cell Carcinoma: A Retrospective, Exploratory Study

Objective: This retrospective study was to identify the outcomes and safety of anlotinib combined with PD-1 blockades in patients with metastatic esophageal squamous cell carcinoma (ESCC). Methods: A retrospective analysis of 87 patients with histologically confirmed metastatic ESCC who received anlotinib plus PD-1 blockades as second-line or later therapy was performed. Efficacy endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Safety was assessed by the incidence of treatment-related adverse events (TRAEs), graded in the principle of CTCAE v5.0. Results: Among 87 evaluable patients, no complete responses were observed, 19 subjects were partial response and 45 achieved stable disease, while 18 had disease progression and 5 were not evaluable for response. Therefore, ORR of the 87 subjects was 21.8% (95% CI: 13.7– 32.0%), and DCR was 73.6% (95% CI: 63.0– 82.4%). Median DoR of the 19 responders was 6.6 months 95% confidence interval (CI): 2.3– 10.9 months. Median PFS and OS for the cohort were 5.5 months (95% CI: 4.1– 6.9 months) and 11.5 months (95% CI: 7.1– 15.9), respectively, the 12-month and 24-month OS rates were 49.0% and 27.6%, respectively. Notably, patients with ESCC who had received prior immunotherapy showed better OS outcomes than those without prior immunotherapy exposure. Toxicity profile analysis demonstrated that the incidence of TRAEs with all grades was 92.0%. Grade ≥ 3 TRAEs occurred in 50.6% of the subjects. Common TRAEs included fatigue (60.9%), hypertension (52.9%), and nausea and vomiting (47.1%), most of which were grade 1– 2 and manageable with supportive measures. Discussion: PD-1 blockades plus anlotinib demonstrated encouraging effectiveness and manageable toxicity in metastatic ESCC, achieving notable disease control and survival benefits compared with historical standards. Future prospective study is needed to confirm the therapeutic benefits and identify the optimal patient selection criteria for this promising combination therapy. Keywords: ESCC, anlotinib, PD-1 blockades, outcomes, safety